-
Neuropsychopharmacology Reports Mar 2024To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis... (Meta-Analysis)
Meta-Analysis
AIM
To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis of double-blind, randomized, placebo-controlled trials of available antidepressants in Japan for older adults with MDD.
METHODS
Outcome measures included response rate (primary), improvement in depressive symptom scale score, remission rate, all-cause discontinuation, discontinuation due to adverse events, and at least one adverse event. A random-effects model was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (95% CI).
RESULTS
Nine double-blind, randomized, placebo-controlled trials (n = 2145) were identified. No study has been conducted in Japan. Our meta-analysis included the following antidepressants: duloxetine, escitalopram, imipramine, sertraline, venlafaxine, and vortioxetine. Antidepressants have significantly higher response rates than placebo (RR [95% CI] = 1.38 [1.04, 1.83], p = 0.02). Antidepressants outperformed placebo in terms of improving depressive symptom scale score (SMD [95% CI] = -0.62 [-0.92, -0.33], p < 0.0001). However, antidepressants were associated with a higher discontinuation rate due to adverse events (RR [95% CI] = 1.94 [1.30, 2.88], p = 0.001) and a higher incidence of at least one adverse event (RR [95% CI] = 1.11 [1.02, 1.21], p = 0.02) compared to placebo. The groups did not differ significantly in terms of remission rate or all-cause discontinuation.
CONCLUSIONS
Our meta-analysis concluded that treatment with antidepressants available in Japan is only weakly recommended for moderate to severe MDD in older adults.
Topics: Humans; Aged; Depressive Disorder, Major; Japan; Antidepressive Agents; Duloxetine Hydrochloride; Venlafaxine Hydrochloride; Randomized Controlled Trials as Topic
PubMed: 38318955
DOI: 10.1002/npr2.12422 -
Medicine Aug 2023Duloxetine, a serotonin-norepinephrine dual reuptake inhibitor, may improve analgesia after total joint arthroplasty (TJA). However, there is still no consensus on its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Duloxetine, a serotonin-norepinephrine dual reuptake inhibitor, may improve analgesia after total joint arthroplasty (TJA). However, there is still no consensus on its effectiveness and safety. We conducted the meta-analysis to investigate the analgesic effect and safety of duloxetine for the treatment of patients received total knee or hip arthroplasty.
METHODS
Pubmed, Cochrane Central Registry for Clinical Trials, Embase, OVID, Web of Science, and Google Scholar were searched using a predetermined search strategy from inception to September 21, 2022. Only randomized controlled trials of duloxetine in treatment of patients after total knee or hip arthroplasty were included. Data collection and extraction, quality assessment, and data analyses were performed according to the Cochrane standards.
RESULTS
A total of 8 randomized controlled trials with 739 patients were included in the literature review of postoperative pain and adverse effects. The result of meta-analysis showed statistically significant lower opioid requirement with duloxetine (P < .05) for the different postoperative period. Duloxetine group had significant reductions in visual analog score for the 24-hour (walking: WMD = -0.98; 95% confidence interval [CI] = -1.69 to -0.26, P = .007; resting: WMD = -1.06; 95%CI = -1.85 to -0.27, P = .008) and 1-week (walking: WMD = -0.96; 95%CI = -1.42 to -0.50, P < .001; resting: WMD = -0.69; 95%CI = -1.22 to -0.16, P = .01); knee injury and osteoarthritis outcome score over 3-month (WMD = 2.94; 95%CI = -0.30 to 6.18, P = .008) and complication (odds ratio = 4.74; 95%CI = 0.23 to 96.56, P = .01) postoperative period compared with the control group. However, no difference on numeric rating scale (P > .05) for the different postoperative period; visual analog score (P > .05) for the 6-week or 3-month and knee injury and osteoarthritis outcome score (P > .05) for the 6-week postoperative period. Furthermore, it did not increase the incidence of adverse effects (odds ratio = 0.87; 95%CI = 0.72 to 1.05, P = .15).
CONCLUSION
Duloxetine could decrease the opioids consumption and relieve early postoperative pain without increasing the risk of adverse medication effects in patients undergoing total knee or hip arthroplasty. Considering the ongoing opioid epidemic, duloxetine could act as a good supplement in multimodal pain management protocol for patients undergoing total joint arthroplasty.
Topics: Humans; Arthroplasty, Replacement, Hip; Duloxetine Hydrochloride; Arthroplasty, Replacement, Knee; Pain Management; Knee Joint; Drug-Related Side Effects and Adverse Reactions; Analgesics, Opioid; Randomized Controlled Trials as Topic
PubMed: 37653762
DOI: 10.1097/MD.0000000000034895 -
Journal of Orthopaedic Surgery and... Jul 2023The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy and safety of duloxetine was conducted. The outcomes of interests were to assess changes in Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), and Clinical Global Impression (CGI). The rate of of adverse events and those leading to therapy discontinuation were also investigated.
MATERIAL AND METHODS
This study followed the 2020 PRISMA guidelines. The literature search started in December 2022 accessing PubMed, Google scholar, Embase, and Scopus databases. All the RCTs investigating the efficacy and safety of daily administration of duloxetine for fibromyalgia were accessed. Studies reporting quantitative data under the outcomes of interest, and including a minimum of 10 patients who completed a minimum of 4 weeks follow-up, were included. Studies on combined pharmacological and non-pharmacological managements for fibromyalgia were not considered.
RESULTS
Data from 3432 patients (11 RCTs) were included. The mean age of the patients was 46.4 ± 10.7 years old, and the mean BMI 25.3 ± 3.2 kg/m. 90% (3089 of 3432 patients) were women. The 60 mg/daily cohort reported the higher FIQ, followed by the 30, 30-60, 120 mg/daily, and placebo groups, while the 60-120 mg /daily group performed the worst results. Concerning the CGI severity scale, placebo resulted in the lowest improvement, and no differences were found in the other groups. Concerning the BPI interference and severity pain scores, the 30-60 mg/daily group reported the worst result, along with the placebo group. The rate of adverse events leading to study discontinuation were lower in the 60-120 group, followed by the 30-60 and 30 mag/daily groups. Duloxetine was superior in all the comparisons to placebo, irrespective of the doses, in all endpoints analysed.
CONCLUSIONS
Duloxetine could help in improving symptoms of fibromyalgia. The dose of duloxetine should be customised according to individual patients. Irrespective of the doses, duloxetine was more effective than placebo in the management of fibromyalgia. The dose of duloxetine must be customised according to individual patients. Level of evidence I Meta-analysis of double-blind RCTs.
Topics: Humans; Female; Adult; Middle Aged; Male; Duloxetine Hydrochloride; Fibromyalgia; Thiophenes; Treatment Outcome; Pain; Randomized Controlled Trials as Topic
PubMed: 37461044
DOI: 10.1186/s13018-023-03995-z -
Journal of Orthopaedic Surgery (Hong... 2023Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with clinical efficacy in chronic pain conditions. In this study, we aim to evaluate the... (Review)
Review
Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with clinical efficacy in chronic pain conditions. In this study, we aim to evaluate the analgesic effect and safety of duloxetine in total knee arthroplasty (TKA). A systematic search was completed on MEDLINE, PsycINFO, and Embase from inception to December 2022 to find relevant articles. We used Cochrane methodology to evaluate the bias of included studies. Investigated outcomes included postoperative pain, opioid consumption, adverse events (AEs), range of motion (ROM), emotional and physical function, patient satisfaction, patient-controlled analgesia (PCA), knee-specific outcomes, wound complications, skin temperature, inflammatory markers, length of stay, and incidence of manipulations. Nine articles involving 942 participants were included in our systematic review. Out of nine papers, eight were randomized clinical trials and one was a retrospective study. The results of these studies indicated the analgesic effect of duloxetine on postoperative pain, which was measured using numeric rating scale and visual analogue scale. Deluxetine was also effective in reducing the morphine requirement and wound complications and enhancing patient satisfaction after surgery. However, the results on ROM, PCA, and knee-specific outcomes were contraventional. Deluxetine was generally safe without serious AEs. The most common AEs included headache, nausea, vomiting, dry mouth, and constipation. Duloxetine may be an effective treatment option for postoperative pain following TKA, but further rigorously designed and well-controlled randomized trials are required.
Topics: Humans; Duloxetine Hydrochloride; Arthroplasty, Replacement, Knee; Retrospective Studies; Pain, Postoperative; Analgesics, Opioid; Randomized Controlled Trials as Topic
PubMed: 37279647
DOI: 10.1177/10225536231177482 -
BMC Musculoskeletal Disorders May 2023Chronic musculoskeletal pain (CMP) is a complex condition that is mainly treated with analgesic drugs. However, antidepressant intervention is also an important factor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic musculoskeletal pain (CMP) is a complex condition that is mainly treated with analgesic drugs. However, antidepressant intervention is also an important factor in the treatment of CMP. Duloxetine is an effective treatment option for patients with CMP as its antidepressant effect. The purpose of this article is to evaluate the efficacy and safety of duloxetine in treating CMP.
DATABASES AND DATA TREATMENT
We searched PubMed, Web of Science, Embase, Cochrane Library from inception to May, 2022. Randomized controlled trials (RCTs) evaluating the efficacy and safety of duloxetine versus placebo in patients with CMP were included. We identified 13 articles and studied a population of 4201 participants in 4 countries.
RESULTS
This meta-analysis showed that the duloxetine has statistically significant compared with the placebo control, benefits on 24-hour average pain, living quality, physical function, and global impressions and there was no difference in the incidence of serious adverse event. In general, duloxetine can improve mood and pain level at the same time.
CONCLUSIONS
This review shows a significant contribution of duloxetine to CMP symptom relief. This meta-analysis improved that duloxetine can significantly reduce the pain level of patients, improve depressive symptoms and global impression, and has no obvious serious adverse reactions. However, additional studies are required to confirm the relationship between psychological diseases and chronic pain and explore their internal links.
Topics: Humans; Duloxetine Hydrochloride; Musculoskeletal Pain; Analgesics; Chronic Pain; Antidepressive Agents
PubMed: 37198620
DOI: 10.1186/s12891-023-06488-6 -
The Cochrane Database of Systematic... May 2023Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain antidepressants may be effective in reducing pain with some benefit in improving patients' global impression of change for certain chronic pain conditions. However, there has not been a network meta-analysis (NMA) examining all antidepressants across all chronic pain conditions.
OBJECTIVES
To assess the comparative efficacy and safety of antidepressants for adults with chronic pain (except headache).
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, AMED and PsycINFO databases, and clinical trials registries, for randomised controlled trials (RCTs) of antidepressants for chronic pain conditions in January 2022.
SELECTION CRITERIA
We included RCTs that examined antidepressants for chronic pain against any comparator. If the comparator was placebo, another medication, another antidepressant, or the same antidepressant at different doses, then we required the study to be double-blind. We included RCTs with active comparators that were unable to be double-blinded (e.g. psychotherapy) but rated them as high risk of bias. We excluded RCTs where the follow-up was less than two weeks and those with fewer than 10 participants in each arm. DATA COLLECTION AND ANALYSIS: Two review authors separately screened, data extracted, and judged risk of bias. We synthesised the data using Bayesian NMA and pairwise meta-analyses for each outcome and ranked the antidepressants in terms of their effectiveness using the surface under the cumulative ranking curve (SUCRA). We primarily used Confidence in Meta-Analysis (CINeMA) and Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) to assess the certainty of the evidence. Where it was not possible to use CINeMA and ROB-MEN due to the complexity of the networks, we used GRADE to assess the certainty of the evidence. Our primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Our secondary outcomes were moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal.
MAIN RESULTS
This review and NMA included 176 studies with a total of 28,664 participants. The majority of studies were placebo-controlled (83), and parallel-armed (141). The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of RCTs was 10 weeks. Seven studies provided no useable data and were omitted from the NMA. The majority of studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. In duloxetine studies, standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that of duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Primary efficacy outcomes Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.69 to 2.17; 16 studies, 4490 participants; moderate-certainty evidence) and continuous pain intensity (standardised mean difference (SMD) -0.31, 95% CI -0.39 to -0.24; 18 studies, 4959 participants; moderate-certainty evidence). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD -0.22, 95% CI -0.39 to 0.06; 4 studies, 1866 participants; moderate-certainty evidence). Mirtazapine (30 mg) had a moderate effect on mood (SMD -0.5, 95% CI -0.78 to -0.22; 1 study, 406 participants; low-certainty evidence), while duloxetine showed a small effect (SMD -0.16, 95% CI -0.22 to -0.1; 26 studies, 7952 participants; moderate-certainty evidence); however it is important to note that most studies excluded participants with mental health conditions, and so average anxiety and depression scores tended to be in the 'normal' or 'subclinical' ranges at baseline already. Secondary efficacy outcomes Across all secondary efficacy outcomes (moderate pain relief, physical function, sleep, quality of life, and PGIC), duloxetine and milnacipran were the highest-ranked antidepressants with moderate-certainty evidence, although effects were small. For both duloxetine and milnacipran, standard doses were as efficacious as high doses. Safety There was very low-certainty evidence for all safety outcomes (adverse events, serious adverse events, and withdrawal) across all antidepressants. We cannot draw any reliable conclusions from the NMAs for these outcomes.
AUTHORS' CONCLUSIONS
Our review and NMAs show that despite studies investigating 25 different antidepressants, the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Evidence for all other antidepressants was low certainty. As RCTs excluded people with low mood, we were unable to establish the effects of antidepressants for people with chronic pain and depression. There is currently no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.
Topics: Adult; Humans; Antidepressive Agents; Chronic Pain; Duloxetine Hydrochloride; Milnacipran; Network Meta-Analysis; Pain Management; Randomized Controlled Trials as Topic
PubMed: 37160297
DOI: 10.1002/14651858.CD014682.pub2 -
International Journal of Surgery... Apr 2023The aim was to evaluate the efficacy and safety of duloxetine for postoperative recovery after total knee arthroplasty. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim was to evaluate the efficacy and safety of duloxetine for postoperative recovery after total knee arthroplasty.
METHODS
The following electronic databases were searched for eligible trials: PubMed, EMBASE, Web of Science, Cochrane Library, VIP, Wanfang Data, and China National Knowledge Infrastructure (CNKI). The search was performed from the inception dates to 10 August 2022. Data extraction and quality assessment were performed by two independent reviewers. Standard mean differences or mean differences with 95% CIs for pooled data were calculated. The primary outcomes were pain, physical function, and analgesic consumption. Secondary outcomes included range of motion (ROM) of the knee, depression, and mental health.
RESULTS
This meta-analysis included 11 studies, reporting on a total of 1019 patients. Results of analyses indicated that duloxetine showed a statistically significant reduction in pain at rest at 3 days, 1 week, 2, and 6 weeks and pain on movement at 5 days, 1 week, 2, 4, 6, and 8 weeks. However, there was no statistical significance in pain at rest and on movement at 24 h, 12 weeks, 6 months, and 12 months. Additionally, duloxetine had a significant improvement in physical function, ROM of the knee at 6 weeks, and emotional function (depression and mental health). Moreover, the cumulative opioid consumption at 24 h in the duloxetine groups was lower than in the control groups. But there was no statistical significance for the cumulative opioid consumption over 7 days between the duloxetine groups and controls.
CONCLUSIONS
In conclusion, duloxetine might reduce pain mainly over a time span of 3 days-8 weeks and lower cumulative opioid consumption within 24 h. In addition, it improved physical function, ROM of the knee with a time span of 1-6 weeks and emotional function (depression and mental health).
Topics: Humans; Arthroplasty, Replacement, Knee; Duloxetine Hydrochloride; Analgesics, Opioid; Knee Joint; Pain, Postoperative
PubMed: 37097617
DOI: 10.1097/JS9.0000000000000230 -
Systematic Reviews Mar 2023Painful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Painful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo treatments in terms of their efficacy and safety in patients with PDPN.
METHODS
Following the PRISMA guidelines, we searched the Cochrane Library, PubMed, and Embase databases for relevant English articles published before January 11, 2021. Treatment efficacy and safety were assessed in terms of pain improvement, patient-reported health-related performance, and patients' quality of life.
RESULTS
We reviewed a total of 7 randomized controlled trials. Regarding pain improvement, duloxetine was more efficacious than placebo (mean difference [MD] - 0.89; 95% confidence interval [CI] - 1.09 to - 0.69; P < .00001). Furthermore, duloxetine significantly improved the patients' quality of life, which was assessed using the Clinical Global Impression severity subscale (MD - 0.48; 95% CI - 0.61 to - 0.36; P < .00001), Patient Global Impression of Improvement scale (MD - 0.50; 95% CI - 0.64 to - 0.37; P < .00001), and European Quality of Life Instrument 5D version (MD 0.04; 95% CI 0.02 to 0.07; P = .0002). Severe adverse events were rare, whereas nausea, somnolence, dizziness, fatigue, constipation, and decreased appetite were common; approximately, 12.6% of all patients dropped out because of the common symptoms.
CONCLUSIONS
Duloxetine is more efficacious than placebo treatments in patients with PDPN. The rarity of severe adverse events indicates that duloxetine is safe. When a 60-mg dose is insufficient, 120 mg of duloxetine may improve PDPN symptoms. Our findings may help devise optimal treatment strategies for PDPN.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021225451.
Topics: Humans; Duloxetine Hydrochloride; Diabetic Neuropathies; Quality of Life; Randomized Controlled Trials as Topic; Pain; Diabetes Mellitus
PubMed: 36945033
DOI: 10.1186/s13643-023-02185-6 -
Frontiers in Pharmacology 2022Treatment of chemotherapy-induced peripheral neuropathy (CIPN) is challenging for clinicians, and many clinical trials and meta-analyses on CIPN are controversial....
Treatment of chemotherapy-induced peripheral neuropathy (CIPN) is challenging for clinicians, and many clinical trials and meta-analyses on CIPN are controversial. There are also few comparisons of the efficacy among drugs used to treat CIPN. Therefore, this systematic review aimed to study the efficacy of drugs in treating CIPN using existing randomized controlled trials. Electronic databases were searched for randomized controlled trials (RCTs) involving any pharmaceutical intervention and/or combination therapy of treating CIPN. Seventeen RCTs investigating 16 drug categories, duloxetine, pregabalin, crocin, tetrodotoxin, venlafaxine, monosialotetrahexosyl ganglioside (GM1), lamotrigine, KA (ketamine and amitriptyline) cream, nortriptyline, amitriptyline, topical (bitter apple) oil, BAK (baclofen, amitriptyline hydrochloride, and ketamine) pluronic lecithin organogel, gabapentin, and acetyl l-carnitine (ALC), in the treatment of CIPN were retrieved. Many of the included RCTs consisted of small sample sizes and short follow-up periods. It was difficult to quantify due to the highly variable nature of outcome indicators. Duloxetine, venlafaxine, pregabalin, crocin, tetrodotoxin, and monosialotetrahexosyl ganglioside exhibited some beneficial effects in treating CIPN. Duloxetine, GM1, and crocin showed moderate benefits based on the evidence review, while lamotrigine, KA cream, nortriptyline, amitriptyline, and topical (bitter apple) oil were not beneficial. Further studies were necessary to confirm the efficacy of gabapentin in the treatment of CIPN because of the controversy of efficacy of gabapentin. Furthermore, BAK topicalcompound analgesic gel only had a tendency to improve the CIPN symptoms, but the difference was not statistically significant. ALC might result in worsening CIPN. Most studies were not of good quality because of small sample sizes. Therefore, standardized randomized controlled trials with large samples were needed to critically assess the effectiveness of these drugs in treating CIPN in the future.
PubMed: 36618919
DOI: 10.3389/fphar.2022.1080888 -
The Cochrane Database of Systematic... Oct 2022Although pain is common in osteoarthritis, most people fail to achieve adequate analgesia. Increasing acknowledgement of the contribution of pain sensitisation has... (Review)
Review
BACKGROUND
Although pain is common in osteoarthritis, most people fail to achieve adequate analgesia. Increasing acknowledgement of the contribution of pain sensitisation has resulted in the investigation of medications affecting pain processing with central effects. Antidepressants contribute to pain management in other conditions where pain sensitisation is present.
OBJECTIVES
To assess the benefits and harms of antidepressants for the treatment of symptomatic knee and hip osteoarthritis in adults.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search was January 2021.
SELECTION CRITERIA
We included randomised controlled trials of adults with osteoarthritis that compared use of antidepressants to placebo or alternative comparator. We included trials that focused on efficacy (pain and function), treatment-related adverse effects and had documentation regarding discontinuation of participants. We excluded trials of less than six weeks of duration or had participants with concurrent mental health disorders.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Major outcomes were pain; responder rate; physical function; quality of life; and proportion of participants who withdrew due to adverse events, experienced any adverse events or had serious adverse events. Minor outcomes were proportion meeting the OARSI (Osteoarthritis Research Society International) Response Criteria, radiographic joint structure changes and proportion of participants who dropped out of the study for any reason. We used GRADE to assess certainty of evidence.
MAIN RESULTS
Nine trials (2122 participants) met the inclusion criteria. Seven trials examined only knee osteoarthritis. Two also included participants with hip osteoarthritis. All trials compared antidepressants to placebo, with or without non-steroidal anti-inflammatory drugs. Trial sizes were 36 to 388 participants. Most participants were female, with mean ages of 54.5 to 65.9 years. Trial durations were 8 to 16 weeks. Six trials examined duloxetine. We combined data from nine trials in meta-analyses for knee and hip osteoarthritis. One trial was at low risk of bias in all domains. Five trials were at risk of attrition and reporting bias. High-certainty evidence found that antidepressants resulted in a clinically unimportant improvement in pain compared to placebo. Mean reduction in pain (0 to 10 scale, 0 = no pain) was 1.7 points with placebo and 2.3 points with antidepressants (mean difference (MD) -0.59, 95% confidence interval (CI) -0.88 to -0.31; 9 trials, 2122 participants). Clinical response was defined as achieving a 50% or greater reduction in 24-hour mean pain. High-certainty evidence demonstrated that 45% of participants receiving antidepressants had a clinical response compared to 28.6% receiving placebo (RR 1.55, 95% CI 1.32 to 1.82; 6 RCTs, 1904 participants). This corresponded to an absolute improvement in pain of 16% more responders with antidepressants (8.9% more to 26% more) and a number needed to treat for an additional beneficial effect (NNTB) of 6 (95% CI 4 to 11). High-certainty evidence showed that the mean improvement in function (on 0 to 100 Western Ontario and McMaster Universities Arthritis Index, 0 = best function) was 10.51 points with placebo and 16.16 points with antidepressants (MD -5.65 points, 95% CI -7.08 to -4.23; 6 RCTs, 1909 participants). This demonstrates a small, clinically unimportant response. Moderate-certainty evidence (downgraded for imprecision) showed that quality of life measured using the EuroQol 5-Dimension scale (-0.11 to 1.0, 1.0 = perfect health) improved by 0.07 points with placebo and 0.11 points with antidepressants (MD 0.04, 95% CI 0.01 to 0.07; 3 RCTs, 815 participants). This is clinically unimportant. High-certainty evidence showed that total adverse events increased in the antidepressant group (64%) compared to the placebo group (49%) (RR 1.27, 95% CI 1.15 to 1.41; 9 RCTs, 2102 participants). The number needed to treat for an additional harmful outcome (NNTH) was 7 (95% CI 5 to 11). Low-certainty evidence (downgraded twice for imprecision for very low numbers of events) found no evidence of a difference in serious adverse events between groups (RR 0.94, 95% CI 0.46 to 1.94; 9 RCTs, 2101 participants). The NNTH was 1000. Moderate-certainty evidence (downgraded for imprecision) showed that 11% of participants receiving antidepressants withdrew from trials due to an adverse event compared to 5% receiving placebo (RR 2.15, 95% CI 1.56 to 2.97; 6 RCTs, 1977 participants). The NNTH was 17 (95% CI 10 to 35).
AUTHORS' CONCLUSIONS
There is high-certainty evidence that use of antidepressants for knee osteoarthritis leads to a non-clinically important improvement in mean pain and function. However, a small number of people will have a 50% or greater important improvement in pain and function. This finding was consistent across all trials. Pain in osteoarthritis may be due to a variety of causes that differ between individuals. It may be that the cause of pain that responds to this therapy is only present in a small number of people. There is moderate-certainty evidence that antidepressants have a small positive effect on quality of life with heterogeneity between trials. High-certainty evidence indicates antidepressants result in more adverse events and moderate-certainty evidence indicates more withdrawal due to adverse events. There was little to no difference in serious adverse events (low-certainty evidence due to low numbers of events). This suggests that if antidepressants were being considered, there needs to be careful patient selection to optimise clinical benefit given the known propensity for adverse events with antidepressant use. Future trials should include alternative antidepressant agents or phenotyping of pain in people with osteoarthritis, or both.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Duloxetine Hydrochloride; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 36269595
DOI: 10.1002/14651858.CD012157.pub2